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Six of eight patients with obsessive-compulsive disorder had an exacerbation of symptoms when given m-chlorophenylpiperazine. Fenfluramine and placebo produced mild improvement. Six patients given intravenous clonidine experienced marked reduction in obsessions. Implications for serotonergic and noradrenergic hypotheses of obsessive-compulsive disorder are discussed.
This study examined whether categorical or dimensional personality disorder variables affected treatment outcome in a sample of 52 patients with obsessive compulsive disorder who followed a standardized cognitive behavior therapy program. Treatment consisted of 12 weekly sessions and was completed by 43 patients. The Structured Clinical Interview for DSM-III-R personality disorders (SCID-II) was taken before the start of treatment by an independent rater. The treatment outcome measures included questionnaires and a Behavioral Assessment Test. Measurements were taken before and after treatment, and at 1 and 6 month follow-up tests. After the first follow-up test, further treatment was provided if clinically indicated. Neither categorical, nor dimensional personality disorder variables affected treatment outcome significantly. The inclusion of drop-outs in the analyses, did not change these results. Therefore, patients with obsessive compulsive disorder and concomitant personality disorder pathology should not be excluded from cognitive or behavior therapy for their obsessive compulsive complaints. Attributing therapy failure to concomitant Axis II pathology should be approached with caution.
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Comorbid psychiatric conditions often complicate the treatment of childhood obsessive-compulsive disorder (OCD). Behavioral treatment of OCD using exposure plus response prevention for a boy with disruptive behavior disorders and two previous unsuccessful medication trials is described. Treatment was adapted to his developmental level, his mother was highly involved in treatment, and a contingency management program contained his disruptive behavior so that he could participate in therapy. Posttreatment and 2- and 6-month follow-up measures indicated marked improvement in OCD symptoms. The possibility of successful behavioral treatment of OCD in medication-free children with disruptive behavior problems is highlighted.
Autism, Asperger's syndrome and other autistic syndromes are developmental brain disorders that cause serious impairments in communication, social interaction, empathy, mood and play. In addition to such deficits, the autistic syndromes involve pathologically high levels of repetitive, stereotypic, ritualistic, compulsive or obsessive behavior, together with extreme resistance to change. According to the Crick-Mitchison theory of the biological function of rapid eye movement sleep, normal brain development in the fetus and infant depends on undisrupted function of a 'reverse learning' mechanism during rapid eye movement sleep. Could abnormalities in this hypothetical reverse learning during rapid eye movement sleep in the fetus explain some aspects of the autistic syndromes? Does the Crick-Mitchison theory suggest if a drug could interfere with rapid eye movement sleep and cross the placental barrier, then that drug might cause developmental brain disorders in the fetus? Should all pregnant women completely avoid caffeine or any agent that might disrupt serotonergic or cholinergic systems?
To determine whether risk factors of ulcerative colitis among Japanese are the same as those observed in other countries, we conducted a case-control study in Japan in 1988-90. Patients selected for the study were receiving financial aid for treatment of the disease; an equal number of population-based controls matched by age and sex were selected. Smoking decreased the risk of the disease (odds ratio = 0.30; 95% confidence interval, 0.16-0.56), and stopping smoking increased the risk (odds ratio compared with those who had never smoked = 1.44; 95% confidence interval, 0.73-2.85). In those who drank alcoholic beverages > or = 5 days a week, disease development was less likely than in others (odds ratio = 0.49; 95% confidence interval, 0.30-0.81). In addition, difficulties in human relations at work, a family history of asthma, a medical history of surgical procedures, and personality traits such as nervousness, anxiety, and obsessive behavior were also considered risk factors. Although some findings are similar to those in former studies, a few findings are different: surgical procedures, occupational status, and a family history of the disease. To clarify whether the differences are consistent will require other case-control studies.
Gilles de la Tourette's syndrome (GTS) is a chronic, familial neuropsychiatric disorder of unknown etiology characterized clinically by the occurrence of motor and vocal tics and by the presence of a variety of neurobehavioral and neurocognitive abnormalities including hyperactivity, self-multilatory behavior, obsessive-compulsive behavior, learning disabilities, and conduct disorder. On the basis of neuropsychological assessments it has been suggested that GTS is associated with greater right than left hemispheric dysfunction which accounts for decrements in visuospatial, visuoconstructional and visuomotor skills in these patients. Recent case studies have demonstrated that extracranial application of electromagnetic fields (EMFs) in the picotesla (pT) range intensity improves visuospatial and visuoperceptive functions in patients with neurodegenerative disorders including Parkinson's disease, multiple sclerosis and Alzheimer's disease. I now present a 6 1/2 year old boy with GTS in whom this treatment modality produced, in addition to symptomatic behavioral improvement, also improvement in visuoconstructional and visuomotor skills as evidenced on various drawing tasks particularly copy of the Rey-Osterrieth Complex Figure, a task which is especially vulnerable to right hemispheric functions. These findings suggest that pT range EMFs may be useful for the treatment of GTS and related disorders and also reverse some of the cognitive impairments associated with the disease which are related to right hemispheric dysfunction and which contribute to learning disabilities in these patients.
Tourette's syndrome (TS), a chronic familial neuropsychiatric disorder of unknown etiology, is characterized clinically by the occurrence of motor and vocal tics and by the presence of a variety of neurobehavioral and neurocognitive abnormalities including hyperactivity, self-mutilatory behavior, obsessive-compulsive behavior, learning disabilities, and conduct disorder. Cognitive deficits related to right hemispheric dysfunction are common in TS patients accounting for decrements in visuospatial, visuoconstructional and visuomotor skills. An 11 year old boy with a 5 years history of TS exhibited during a routine neuropsychological assessment an unusual visuoconstructional disorder which previously has been observed in dyslexic children. Specifically, when instructed to draw a bicycle from memory, he drew spontaneously a design executed from the perspective of a bird's eye view. After receiving a 20 minute treatment session with picotesla range electromagnetic fields (EMFs) applied extracranially, this visuocontructional disorder was spontaneously reversed and he drew an elaborate and detailed bicycle positioned in profile. A placebo EMF treatment, which was administered prior to magnetic therapy, had no effect on this child's visuoconstructional disorder. During the ensuing week there was a marked reduction in the child's hyperactive behavior with attentuation of motor tics. Spontaneous drawing of a bicycle a week after the administration of magnetic therapy was executed in profile although some elements were presented from a bird's eye view. This case demonstrates the potential impact of treatment with picotesla EMFs in reversing specific cognitive deficits in TS related to right posterior hemispheric dysfunction.
Tic disorders are frequent in childhood, varying from transient motor tics over multiple chronic tic disorders to full-blown Gilles de la Tourette syndrome (GTS). GTS is genetically determined. In affected families, relatives of the patient(s) with GTS may show minor symptoms only. The clinical picture is extremely variable, extending from the well known motor tics over complex compulsive obsessive behavior to purely sensory tics. The optimal treatment today is the use of dopamine antagonists.
We reported a patient with choreic movements, emotional lability, and compulsive-obsessive behavior that developed 4 weeks after onset of fever and lasted for several years. There was no evidence of streptococcal infection or rheumatic fever. T2-weighted MRI showed hyperintense lesions in the bilateral caudate nuclei and putamina. A diagnosis of focal encephalitis was made according to initial fever, convulsion, and CSF pleocytosis. Treatments with haloperidol and prednisolone were effective in some degree. The neurobehavioral syndrome as well as the involuntary movements in this patient can be attributed to the striatal damage, which may disrupt the basal ganglia-limbic-frontal lobe tracts. A symptomatic similarity between the syndrome in this patient and chorea minor suggests a striatal damage in chorea minor, where the causative lesions remain unknown.
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To evaluate serotonergic (5-hydroxytryptamine) function in obsessive-compulsive disorder, behavioral and neuroendocrine responses to m-chlorophenylpiperazine (m-CPP; 0.5 mg/kg orally) and fenfluramine hydrochloride (60 mg orally) were examined in 20 patients and 10 healthy controls under double-blind, placebo-controlled conditions. Following m-CPP, but not fenfluramine or placebo, 55% (11/20) of the patients with obsessive-compulsive disorder experienced a transient exacerbation of obsessive-compulsive disorder. Prolactin response was blunted in patients following m-CPP but not following fenfluramine. Patients with greater behavioral response to m-CPP had smaller prolactin responses. Cortisol response to m-CPP and fenfluramine did not significantly differ between the groups. Behavioral and neuroendocrine responses appeared divergent. This does not suggest simply upregulation or downregulation of 5-hydroxytryptamine receptors, but rather complex mechanisms involving multiple neurotransmitter and neuromodulator systems.
To evaluate noradrenergic (NE) function in obsessive-compulsive disorder (OCD), behavioral, physiological, and neuroendocrine responses to the alpha 2-adrenergic agonist clonidine were examined in 18 patients with OCD and 10 healthy subjects. Subjects received single i.v. doses of 2 micrograms/kg of clonidine administered under double-blind, placebo-controlled, random-assignment conditions. Following clonidine, but not following placebo, patients transiently experienced a significant reduction of obsessions and compulsions. Significant drowsiness and a reduction in anxiety were also noted, but the antiobsessional effect appeared independent of the soporific and antianxiety effects. Growth hormone (GH), cortisol, and 3-methoxy-4-hydroxyphenylglycol responses to clonidine did not differentiate patients from healthy controls. Blood pressure and pulse in response to clonidine did not differ between groups. Improvement in OCD symptoms after clonidine significantly correlated with GH response to clonidine, suggesting specific noradrenergic mediation. This finding lends only partial support for a primary defect of noradrenergic function in OCD.
The lifetime prevalence of eating disorders and pathologic gambling was assessed in first-degree relatives of subjects with obsessive-compulsive disorder (OCD) and well controls. There were no significant differences between the groups. The authors conclude that eating disorder and pathologic gambling have no familial relationship to OCD.
Treatment with fluoxetine hydrochloride was compared with treatment with clomipramine hydrochloride in two groups of patients with obsessive-compulsive disorder using two different experimental designs. In the first group of 11 patients with obsessive-compulsive disorder studied using a randomized, double-blind, crossover design, treatment with fluoxetine for 10 weeks was found to produce therapeutic effects similar to treatment with clomipramine for 10 weeks. There were significantly fewer total side effects reported during fluoxetine than clomipramine treatment. Drug tapering and placebo substitution in the 4-week crossover interval phase led to substantial relapses in obsessive-compulsive disorder symptoms and depression. Furthermore, responses to the second drug took as long to occur as responses to the first drug, although both drugs are thought to act by a common mechanism, serotonin uptake inhibition. A second group of 21 patients with obsessive-compulsive disorder that had been previously stabilized on clomipramine treatment with at least partial benefit were crossed over to fluoxetine treatment in a double-blind fashion. After 10 weeks of fluoxetine administration, most patients manifested behavioral rating scores of obsessive-compulsive disorder and depressive symptoms that were comparable with precrossover ratings completed during clomipramine treatment. A significant exacerbation in obsessive-compulsive disorder and depression ratings as well as a similar lag in therapeutic efficacy were also noted in this second cohort of patients with obsessive-compulsive disorder. Platelet 5-HT concentrations were reduced 95% during both clomipramine and fluoxetine treatment periods. These results suggest that fluoxetine may represent a viable alternative to clomipramine in the treatment of obsessive-compulsive disorder, although further studies with larger sample sizes are needed.
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Obsessive-Compulsive Disorders (OCD) were once considered a relatively rare condition and highly refractory to treatment. Behavioral treatments consisting primarily of various methods of exposure and response prevention are reported to be approximately 70% effective in treating this condition that may affect 2 to 3% of the population and, in many cases, the effectiveness of these interventions persists over a number of years. However much remains to be done in refining these strategies and determining which patients are most likely to respond to these interventions.
The aim of the study was to identify factors associated with treatment compliance and clinical improvement when obsessive compulsive disorder is treated with graded exposure and response prevention. The sample consisted of all patients with a diagnosis of obsessive compulsive disorder admitted over a 3-year period to a unit specialising in behavioral treatment. All subjects were diagnosed using reliable diagnostic criteria and all were followed-up for 12 months. A range of social and clinical variables was examined using stepwise regression analysis. Treatment compliance was associated with being employed during treatment and living with one's family. Clinical improvement was associated with never having been treated previously, being employed during treatment, having a fear of contamination, having overt ritualistic behaviour, the absence of depression and living with one's family.